77 articles - From Saturday Jan 01 2022 to Friday Jan 07 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
meta-analyses and systematic reviews
| Blood Cancer J |
Efficacy of front-line immunochemotherapy for follicular lymphoma: a network meta-analysis of randomized controlled trials. Bendamustine was a better chemotherapy backbone than CHOP either with maintenance (R-Benda-R vs R-CHOP-R, HR |
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
Chronic myelomonocytic leukemia: 2022 update on diagnosis, risk stratification, and management. The MMM stratifies CMML patients into four groups: high (=3 risk factors), intermediate-2 (2 risk factors), intermediate-1 (1 risk factor), and low (no risk factors), with median survivals of 16, 31, 59, and 97 |
Cytogenetic risk classification maintains its prognostic significance in transplanted FLT3-ITD mutated acute myeloid leukemia patients: On behalf of the acute leukemia working party/European society of blood and marrow transplantation. OS was significantly lower in patients with adverse risk cytogenetics compared with patients with favorable risk cytogenetics (HR = 1.74, 95% CI, 1.16-2.61; p = |
Gilteritinib clinical activity in relapsed/refractory FLT3 mutated acute myeloid leukemia previously treated with FLT3 inhibitors. Survival was longest in patients who obtained a CR, particularly a cMRD (clinical minimal or measurable residual disease) negative response; this remained significant after censoring at the time of stem cell transplant. The mitogen-activated protein kinase pathway activating mutations that are known for gilteritinib resistance (NRAS, KRAS, and PTPN11) had lower CRc (35% vs 60.5%) and lower median overall survival than patients' whose leukemia did not express these mutations (4.9 months vs 7.8 months) (HR 2.4; 95% CI 1. 5.4) p value <.01. |
HLA 1-3 antigen-mismatched related peripheral blood stem cells transplantation using low-dose antithymocyte globulin versus unrelated cord blood transplantation. The incidences of relapse and chronic GVHD were comparable between these donors. In conclusion, CBT-no ATG may be a better alternative than HLA-mismatched related donor PBSCT using low-dose ATG. Notably, HLA 2-3 antigen mismatch-related transplantation with low-dose ATG had significant adverse effects on transplantation outcomes. |
Impact of achieving a complete response to initial therapy of multiple myeloma and predictors of subsequent outcome. We evaluated 1869 newly diagnosed MM patients who had = 2 monoclonal protein immunofixation studies in the serum and urine available within 24 |
Improved outcomes among newly diagnosed patients with FMS-like tyrosine kinase 3 internal tandem duplication mutated acute myeloid leukemia treated with contemporary therapy: Revisiting the European LeukemiaNet adverse risk classification. In multivariable cox proportional hazards model of patients receiving intensive or low-intensity induction regimens, FLT3 mutations did not have prognostic significance. The use of allogeneic SCT in CR1 for patients with FLT3 mutations appears to improve survival, particularly in those with ELN adverse risk disease. Overall, this data highlights the changing prognostic impact of FLT3 mutations in a contemporary era with appropriate use of induction therapy combined with targeted agents and allogenic SCT. |
Sustained, complete response to pexidartinib in a patient with CSF1R-mutated Erdheim-Chester disease. The patient was treated with pexidartinib, a CSF1R inhibitor, and has had a complete clinical and metabolic response lasting more than 1.5 years to date. To our knowledge, this is the first report to describe successful treatment of a patient with ECD by using an agent that specifically targets CSF1R. This case also highlights the critical role of individualized molecular profiling to identify novel therapeutic targets in ECD. |
The insertion site is the main risk factor for central venous catheter-related complications in patients with hematologic malignancies. The strongest risk factor for the endpoints CRBSI, CLABSI, and LI was the insertion site. However, SCV insertion was a risk factor for LI (p = .001, HR: 2.0), insertion in the IJV a risk factor for CLABSI (p = .044, HR: 2.7) and CRBSI (p = .036, HR: 5.4). These results demonstrate a differential effect of the insertion site of CVC in neutropenic patients with a significantly reduced frequency of CVC-related blood stream infections in SCV-CVC. |
TLR8/TLR7 dysregulation due to a novel TLR8 mutation causes severe autoimmune hemolytic anemia and autoinflammation in identical twins. G572V mutation causes impaired stability of the TLR8 protein, cross-reactivity to TLR7 ligands and reduced ability of TLR8 to attenuate TLR7 signaling. This imbalance toward TLR7-dependent signaling leads to increased pro-inflammatory responses, such as nuclear factor- |
| Blood |
CD45-targeted antibody-drug-conjugate successfully conditions for allogeneic hematopoietic stem cell transplantation. When CD45-ADC was combined with pre-transplant TBI (50cGy) and post-transplant Rapamycin, Cytoxan or a JAK inhibitor, 90-100% of recipients achieved stable chimerism (mean: 77%, 59%, 78%, respectively). At a higher dose (5mg/kg), CD45-ADC as a single agent was sufficient for rapid, high level multi-lineage chimerism sustained through the 22 weeks observation period. Therefore, CD45-ADC has potential utility to confer the benefit of fully myeloablative conditioning but with substantially reduced toxicity when given as a single agent or at lower doses in conjunction with reduced intensity conditioning. |
Modulation of the HIF2-NCOA4 axis in enterocytes attenuates iron loading in a mouse model of hemochromatosis. These analyses revealed that the intestinal and systemic response to iron deficiency was not altered following disruption of intestinal NCOA4. However, in a mouse model of hemochromatosis, ablation of intestinal NCOA4 was protective against iron overload. Therefore, NCOA4 can be selectively targeted for the management of iron overload disorders without disrupting the physiological processes involved in the response to systemic iron deficiency. |
The journey of neutropoiesis: how complex landscapes in bone marrow guide continuous neutrophil lineage determination. Cell fate decisions both at the level of proliferation and differentiation are enforced through expression of lineage-determining transcription factors (LDTFs) and their interactions, that are influenced by both intrinsic (intracellular) as well as extrinsic (extracellular) mechanisms. Neutrophil homeostasis is subjected to positive feedback loops, stemming from the gut microbiome, as well as negative feedback loops resulting from the clearance of apoptotic neutrophils by mature macrophages. Finally, the cellular kinetics regarding the replenishing of the mature neutrophil pool is discussed in light of recent, contradictory data. |
| Blood Adv |
A new murine model of Barth Syndrome neutropenia links TAFAZZIN deficiency to increased ER stress induced apoptosis. Contrary to our hypothesis, we did not identify any significant differences in neutrophil development or neutrophil function across a variety of assays including phagocytosis, and the production of cytokines or reactive oxygen species. However, transcriptomic analysis of the TAFAZZIN-deficient neutrophil progenitors demonstrated an upregulation of markers of endoplasmic reticulum stress and confirmatory testing demonstrated that the TAFAZZIN-deficient cells had increased sensitivity to certain ER stress mediated and non ER stress mediated triggers of apoptosis. While the link between increased sensitivity to apoptosis and the variably penetrant neutropenia phenotype seen in some Barth syndrome patients remains to be clarified, our studies and new model system set a foundation for further investigation. |
A Randomized Phase 2 Trial of Azacitidine ± Durvalumab as First-line Therapy for Higher-Risk Myelodysplastic Syndromes. In summary, combining durvalumab and azacitidine in patients with HR-MDS was feasible, but with more toxicities and without significant improvement in clinical outcomes over azacitidine alone. ClinicalTrials. gov: NCT02775903. |
A somatic UBA2 variant preceded ETV6-RUNX1 in the concordant BCP-ALL of monozygotic twins. Quantification of the UBA2 deletion by dPCR surprisingly indicated it persisted in remission. This, for the first time to our knowledge, provided evidence of a UBA2 variant preceding the well-established initiating event ETV6-RUNX1. Further, we suggest the UBA2 deletion exerted a leukemia predisposing effect and that its essential role in SUMOylation, regulating nearly al physiological and pathological cellular processes such as DNA-repair by non-homologous end joining, may hold a mechanistic explanation for the predisposition. |
Blinatumomab In pediatric relapsed/refractory B-cell acute lymphoblastic leukemia: RIALTO expanded access study final analysis. These findings support the use of blinatumomab as a safe and efficacious treatment for pediatric R/R B-ALL. (ClinicalTrials. gov identifier NCT02187354). |
Extent of intravital contraction of arterial and venous thrombi and pulmonary emboli. In pulmonary emboli, the extent of contraction was significantly lower than in the venous head, but was similar to the body and tail, suggesting that the emboli originate from the younger portion(s) of venous thrombi. The extent of contraction in arterial cerebral thrombi was significantly higher than in the younger parts of venous thrombi (body, tail) and pulmonary emboli, but was indistinguishable from the older part (head). A novel tool, named the "contraction ruler," has been developed to use the composition of ex vivo thrombi to assess the extent of their intravital contraction, which contributes to the pathophysiology of thromboembolism. |
Hypermethylation at the CXCR5 gene locus limits trafficking potential of CD8+ T cells into B-cell follicles during HIV-1 infection. Transcriptional factor footprints analysis revealed enrichment of transforming growth factors (TGFs) at the TSS of fCD8s. In-vitro stimulation of non-fCD8s with recombinant TGF-ß resulted in significant increase in CXCR5 expression (fCD8s). Thus, this study identifies TGF-ß signaling as a viable strategy for increasing fCD8s frequencies in follicular areas of the LN where they are needed to eliminate HIV infected cells, with implications for HIV cure strategies. |
Inflammasome activation in neutrophils of patients with severe COVID-19. Time-lapse microscopy in LPS-stimulated neutrophils from fluorescent ASC reporter mice showed that ASC speck formed transiently and at the microtubule organizing center, long before NET release. Our study shows that ASC speck is present in neutrophils from COVID-19 patients with respiratory failure and that it forms early in NETosis. Our findings suggest that inhibition of neutrophil inflammasomes may be beneficial in COVID-19. |
Lymphocyte Cytosolic Protein 1 (L-plastin) I232F Mutation Impairs Granulocytic Proliferation and Causes Neutropenia. Confocal imaging and subcellular fractionation revealed diffuse intracellular localization of LCP1, but only the mutant form was found in the nucleus. We conclude that LCP1 is a new gene involved in granulopoiesis, and the missense variant LCP1 I232F leads to neutropenia and granulocytic dysplasia with aberrant actin dynamics. Our work supports a model of neutropenia due to aberrant actin regulation. |
Lysosomal iron recycling in mouse macrophages is dependent upon both reductases LcytB and Steap3. We show transcript expression of LcytB and Steap3 is decreased in macrophages exposed to Escherichia coli pathogen UTI89 supporting a role for these reductases in regulating iron availability for pathogens. We further show that loss of LcytB and Steap3 in macrophages infected with UTI89, led to increased intracellular UTI89 proliferation suggesting that the endolysosomal system is retaining Fe3+ that can be used for intravesicular pathogen proliferation. Together, our findings reveal an important role for both LcytB and Steap3 in macrophage iron recycling and suggest that limiting iron recycling by decreasing expression of endolysosomal reductases is an innate immune response to protect against pathogen proliferation and sepsis. |
M-CSFR/CSF1R signaling regulates myeloid fates in zebrafish via distinct action of its receptors and ligands. Our single-cell RNA sequencing analysis of adult whole kidney marrow (WKM) hematopoietic cells suggests that csf1rb is expressed mainly by blood and myeloid progenitors and that the expression of csf1ra and csf1rb is non-overlapping. We point out differentially expressed genes important in hematopoietic cell differentiation and immune response in selected WKM populations. Our findings could improve the understanding of myeloid cell function and lead to the further study of CSF1R pathway deregulation in disease, mostly in cancerogenesis. |
Pembrolizumab plus dinaciclib in patients with hematologic malignancies: the phase 1b KEYNOTE-155 study. These findings demonstrate activity with combination pembrolizumab plus dinaciclib and suggest that a careful and comprehensive approach to explore anti-PD-1 and CDK9 inhibitor combinations is warranted. Clinical trial registration: ClinicalTrials. gov, NCT02684617. |
Platelet SHARPIN regulates platelet adhesion and inflammatory responses through associations with aIIbß3 and LUBAC. Platelets lacking SHARPIN also showed reduced NF- |
Post-Hematopoietic Stem Cell Transplantation Immune-Mediated Anemia: A Literature Review and Novel Therapeutics. It is crucial to identify the driving etiology of post-HCT anemia in order to prevent and treat this condition. This requires a comprehensive understanding of the mechanism of anemia in blood group incompatible HCT, and the temporal association between HCT and anemia. In this review, we summarized the literature on post-HCT immune-mediated anemia with a focus on ABO and non-ABO blood group incompatibility, described the underlying mechanism of anemia, and outlined preventive and treatment approaches. |
SORT1/LAMP2-mediated Extracellular Vesicle Secretion and Cell Adhesion Are Linked to Lenalidomide Resistance in Multiple Myeloma. Silencing of these genes caused decreased EV secretion and loss of cell adhesion in the resistant cells, resulting in increased sensitivity to lenalidomide. Analysis of publicly available transcriptome data confirmed the relationship between genes related to EV secretion and cell adhesion and patient prognosis. Together, our findings reveal a novel mechanism of lenalidomide resistance in MM mediated by EV secretion and cell adhesion via SORT1 and LAMP2. |
T-replete HLA-matched Grafts vs T-depleted HLA-mismatched Grafts in Inborn Errors of Immunity. Grade III-IV aGvHD was observed in 8% of T-replete marrow, 7% of T-replete PBSC, 14% of T-replete CB and 2% of T-depleted PBSC (p=0.73). Higher incidence of viraemia (p<0.001) and delayed CD3 reconstitution (p=0.003) were observed after T-depleted graft HCT. These data indicate that mismatched donor transplant after TCR aß and CD19 depletion represents an excellent alternative for younger children with IEI in need of an allograft. |
| Haematologica |
Prospects in the management of patients with follicular lymphoma beyond first-line therapy. The current landscape is likely to continue evolving rapidly with other effective agents emerging (notably bispecific antibodies and other targeted therapies), and multiple combinations being evaluated. It is hoped that new treatments under development will achieve longer progression-free intervals and minimize toxicity. A better understanding of disease biology and the mechanisms of these different agents should provide further insights to select the optimal therapy at each stage of disease. |
Time for an individualized approach to first-line management of follicular lymphoma. However, in a significant minority (~20%) who experience early progression or histological transformation after treatment, the disease no longer has an indolent behavior. This review looks at the development of prognostic indices, staging and therapies for follicular lymphoma, identifying where the data can, and cannot, guide the multidisciplinary team to determine an individualized approach to first-line therapy. A nuanced patient- and disease-specific approach is necessary to maximize disease response and survival while minimizing therapeutic toxicity. |
| Lancet Haematol |
Efficacy and safety of itacitinib versus placebo in combination with corticosteroids for initial treatment of acute graft-versus-host disease (GRAVITAS-301): a randomised, multicentre, double-blind, phase 3 trial. Interpretation The observed improvement in ORR at day 28 with the addition of itacitinib versus placebo to corticosteroids did not reach the prespecified significance level. Further studies might provide additional insight into the utility of selective JAK1 inhibition for the treatment of acute GVHD. Funding Incyte. |
Hydroxyurea for primary stroke prevention in children with sickle cell anaemia in Nigeria (SPRING): a double-blind, multicentre, randomised, phase 3 trial. However, secondary analyses suggest that the moderate-dose group could lower incidence rates for all-cause hospitalisations. These findings provide an evidence-based guideline for the use of low-dose hydroxyurea therapy for children with sickle cell anaemia at risk of stroke. Funding National Institute of Neurological Disorders and Stroke. |
Survival by age in paediatric and adolescent patients with Hodgkin lymphoma: a retrospective pooled analysis of children's oncology group trials. Interpretation Adolescents (=15 years) treated on COG Hodgkin lymphoma trials had worse event-free survival and increased risk of death compared with children (<15 years). Our findings highlight the need for prospective studies to examine tumour and host biology, and to test novel therapies across the age spectrum. Funding National Institutes of Health, St Baldrick's Foundation, and Lymphoma Research Foundation. |
Symptom burden and quality of life in patients with high-risk essential thrombocythaemia and polycythaemia vera receiving hydroxyurea or pegylated interferon alfa-2a: a post-hoc analysis of the MPN-RC 111 and 112 trials. However, symptom burden worsened between 3 and 12 months in patients with low baseline symptom burden (patients treated with pegylated interferon alfa-2a: mean total symptom score change 3·2, 95% CI 0·9 to 5·4; patients treated with hydroxyurea: 3·4, 0·6 to 6·2). Interpretation Results can inform treatment decisions, including treatment timing and goals in managing essential thrombocythaemia and polycythaemia vera, because measuring symptom burden from the patient perspective is crucial to understanding treatment efficacy and tolerability. Funding US National Cancer Institute of the National Institutes of Health, and Roche Genentech. |
| Leukemia |
Daratumumab plus lenalidomide and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: frailty subgroup analysis of MAIA. Improved rates of complete response or better and minimal residual disease (10 -5 ) negativity were observed for D-Rd across subgroups. The most common grade 3/4 treatment-emergent adverse event in non-frail and frail patients was neutropenia (non-frail, 45.4% [D-Rd] and 37.2% [Rd]; frail, 57.7% and 33.1%). These findings support the clinical benefit of D-Rd in transplant-ineligible NDMM patients enrolled in MAIA, regardless of frailty status. |
| Thromb Haemost |
Effectiveness and safety of oral anticoagulants in the treatment of acute venous thromboembolism: A nationwide comparative cohort study in France. Apixaban was associated with superior safety and effectiveness than VKAs. All-cause mortality was lower in both DOACs than VKAs. Our results support recommendations to use DOACs over VKAs for the treatment of VTE. |
Pharmacodynamic profiles of dual-pathway inhibition with or without clopidogrel vs dual antiplatelet therapy in patients with atherosclerotic disease. Compared with DAPT, DPI does not result in any differences in platelet-mediated global thrombogenicity, but reduces thrombin generation. These PD observations support that modulating thrombin generation by means of factor Xa inhibition in adjunct to antiplatelet therapy provides effective antithrombotic effects, supporting the efficacy and safety findings of DPI observed in clinical. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Blood |
Vasculopathy in COVID-19. Knowledge of vascular pathogenesis in COVID-19 has also informed therapeutic approaches that may control its systemic sequelae. Since our understanding of vascular response in COVID-19 continues to evolve, we will consider areas of controversy, such as the extent to which SARS-CoV-2 directly infects endothelium and the degree to which vascular responses to SARS-CoV-2 are unique or common to those of other viruses capable of causing severe respiratory disease. This conceptual framework describing how SARS-CoV-2 infection affects endothelial inflammation, prothrombotic transformation, and barrier dysfunction will provide a context for interpreting new information as it arises addressing the vascular complications of COVID-19. |
| Haematologica |
| Lancet Haematol |
Letters to the editors and authors’ replies
| Am J Hematol |
| Blood |
| Blood Cancer J |
| Lancet Haematol |
all remaining publications eg case reports, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| Haematologica |
| Lancet Haematol |
| Leukemia |